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PE20212302A1 - Inhibidores de apol1 y sus metodos de uso - Google Patents

Inhibidores de apol1 y sus metodos de uso

Info

Publication number
PE20212302A1
PE20212302A1 PE2021000896A PE2021000896A PE20212302A1 PE 20212302 A1 PE20212302 A1 PE 20212302A1 PE 2021000896 A PE2021000896 A PE 2021000896A PE 2021000896 A PE2021000896 A PE 2021000896A PE 20212302 A1 PE20212302 A1 PE 20212302A1
Authority
PE
Peru
Prior art keywords
independently selected
thiol
groups
branched
methods
Prior art date
Application number
PE2021000896A
Other languages
English (en)
Inventor
Michael Brodney
Kevin Gagnon
Kan-Nian Hu
Ales Medek
Peter Rose
Yi Shi
Muna Shrestha
Faith Witkos
Jingrong Cao
Jon H Come
Leslie A Dakin
Francois Denis
Warren A Dorsch
Anne Fortier
Martine Hamel
Elaine Krueger
Brian Ledford
Suganthini S Nanthakumar
Olivier Nicolas
Camil Sayegh
Timothy J Senter
Tiansheng Wang
Original Assignee
Vertex Pharma
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Vertex Pharma filed Critical Vertex Pharma
Publication of PE20212302A1 publication Critical patent/PE20212302A1/es

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/4025—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil not condensed and containing further heterocyclic rings, e.g. cromakalim
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/66—Phosphorus compounds
    • A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/69—Boron compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/695—Silicon compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
    • C07F5/02—Boron compounds
    • C07F5/025—Boronic and borinic acid compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
    • C07F7/02—Silicon compounds
    • C07F7/08—Compounds having one or more C—Si linkages
    • C07F7/0803—Compounds with Si-C or Si-Si linkages
    • C07F7/081—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te
    • C07F7/0812—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te comprising a heterocyclic ring
    • C07F7/0814—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te comprising a heterocyclic ring said ring is substituted at a C ring atom by Si
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
    • C07F7/02—Silicon compounds
    • C07F7/08—Compounds having one or more C—Si linkages
    • C07F7/0803—Compounds with Si-C or Si-Si linkages
    • C07F7/081—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te
    • C07F7/0812—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te comprising a heterocyclic ring
    • C07F7/0816—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te comprising a heterocyclic ring said ring comprising Si as a ring atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/46—Phosphinous acids [R2POH], [R2P(= O)H]: Thiophosphinous acids including[R2PSH]; [R2P(=S)H]; Aminophosphines [R2PNH2]; Derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6564—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
    • C07F9/6581—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms
    • C07F9/6584—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms having one phosphorus atom as ring hetero atom
    • C07F9/65842—Cyclic amide derivatives of acids of phosphorus, in which one nitrogen atom belongs to the ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/05—Isotopically modified compounds, e.g. labelled
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/13—Crystalline forms, e.g. polymorphs

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Urology & Nephrology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Thiazole And Isothizaole Compounds (AREA)

Abstract

Referido a un compuesto de formula I, en donde: cada R1 se selecciona, de modo independiente, de grupos halogeno, hidroxi, tiol, amino, entre otros; cada R2 se selecciona, de modo independiente, de grupos halogeno, hidroxi, tiol, ciano, entre otros; m se selecciona de 0, 1, 2, 3 y 4; n se selecciona de 0, 1, 2, 3, 4 y 5; (v) Y se selecciona de grupos alquilo divalentes C1-C8 lineales y ramificados ciclicos, grupos alcoxi divalentes C1-C8 lineales y ramificados, entre otros; cada de R3 y R4 se selecciona, de modo independiente, de H, hidroxi, tiol, entre otros; cada de R5 y R6 se selecciona, de modo independiente, de H, tiol, amino, entre otros; cada de R7, R8 y R9 se selecciona, de modo independiente, de H, grupos alquilo C1-C6 lineales, ramificados y ciclicos, grupos hidroxialquilo C1-C6 lineales, ramificados y ciclicos, entre otros; sus sales farmaceuticamente aceptables, solvatos y derivados deuterados de los mismos. Estos compuestos son inhibidores de la actividad de apolipoproteina L1 (APOL1). Tambien se refiere a metodos de preparacion de dichos compuestos, formas en estado solido de ellos, composicion farmaceutica que los comprenden y metodos que los usan, incluyendo el uso en el tratamiento de glomeruloesclerosis segmentaria focal (FSGS) y/o enfermedad renal no diabetica (NDKD).
PE2021000896A 2018-12-17 2019-12-17 Inhibidores de apol1 y sus metodos de uso PE20212302A1 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201862780667P 2018-12-17 2018-12-17
PCT/US2019/066746 WO2020131807A1 (en) 2018-12-17 2019-12-17 Inhibitors of apol1 and methods of using same

Publications (1)

Publication Number Publication Date
PE20212302A1 true PE20212302A1 (es) 2021-12-10

Family

ID=69182627

Family Applications (1)

Application Number Title Priority Date Filing Date
PE2021000896A PE20212302A1 (es) 2018-12-17 2019-12-17 Inhibidores de apol1 y sus metodos de uso

Country Status (24)

Country Link
US (3) US11618746B2 (es)
EP (1) EP3897833A1 (es)
JP (1) JP7573528B2 (es)
KR (1) KR20210116483A (es)
CN (1) CN113453760B (es)
AR (1) AR116913A1 (es)
AU (1) AU2019405477B2 (es)
CA (1) CA3121910A1 (es)
CL (1) CL2021001561A1 (es)
CO (1) CO2021009053A2 (es)
CR (1) CR20210383A (es)
DO (1) DOP2021000116A (es)
EC (1) ECSP21052184A (es)
IL (2) IL283592B2 (es)
JO (3) JOP20210129A1 (es)
MA (1) MA54538A (es)
MX (1) MX2021007152A (es)
PE (1) PE20212302A1 (es)
SA (1) SA521422270B1 (es)
SG (1) SG11202105769XA (es)
TW (1) TWI848031B (es)
UA (1) UA128375C2 (es)
UY (1) UY38514A (es)
WO (1) WO2020131807A1 (es)

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US12116343B2 (en) 2020-01-29 2024-10-15 Vertex Pharmaceuticals Incorporated Inhibitors of APOL1 and methods of using same
US20210246121A1 (en) * 2020-02-04 2021-08-12 Vertex Pharmaceuticals Incorporated Solid forms of apol1 inhibitor and methods of using same
JP7776430B2 (ja) * 2020-03-06 2025-11-26 バーテックス ファーマシューティカルズ インコーポレイテッド Ａｐｏｌ－１依存性巣状分節性糸球体硬化症を治療する方法
US20230150980A1 (en) 2020-04-22 2023-05-18 Anima Biotech Inc. Collagen 1 translation inhibitors and methods of use thereof
HUP2200468A1 (hu) 2020-04-29 2023-03-28 X Chem Zrt IAP antagonisták és gyógyászati alkalmazásuk
IL297849A (en) 2020-05-07 2023-01-01 Rambam Med Tech Ltd The composition for use in the treatment of apol1-related disease
AU2021289750A1 (en) 2020-06-12 2023-02-02 Vertex Pharmaceuticals Incorporated Solid forms of APOL1 inhibitor and using the same
JP2023529216A (ja) 2020-06-12 2023-07-07 バーテックス ファーマシューティカルズ インコーポレイテッド Ａｐｏｌ１の阻害剤及びその使用
CA3185604A1 (en) 2020-06-12 2021-12-16 Vertex Pharmaceuticals Incorporated Inhibitors of apol1 and use of the same
MX2023002269A (es) 2020-08-26 2023-05-16 Vertex Pharma Inhibidores de apol1 y metodos para usar los mismos.
MX2024002229A (es) 2021-08-26 2024-05-15 Vertex Pharma Formas solidas de inhibidores de apolipoproteina l1 (apol1) espirotriciclicos y metodos de uso de las mismas.
US20250084094A1 (en) 2021-11-30 2025-03-13 Vertex Pharmaceuticals Incorporated Spirocyclic inhibitors of apol1 and methods of using same
US20230203000A1 (en) 2021-11-30 2023-06-29 Vertex Pharmaceuticals Incorporated Inhibitors of apol1 and methods of using same
WO2023154344A1 (en) 2022-02-08 2023-08-17 Vertex Pharmaceuticals Incorporated 2-methyl-4',5'-dihydrospiro[piperidine-4,7'-thieno[2,3-c]pyran] derivatives as inhibitors of apol1 and methods of using same
CN119013281A (zh) 2022-02-08 2024-11-22 弗特克斯药品有限公司 作为apol1抑制剂的4'，5'-二氢螺[哌啶-4，7'-噻吩并[2，3-c]吡喃]衍生物和其使用方法
CN118984821A (zh) 2022-02-08 2024-11-19 弗特克斯药品有限公司 作为apol1抑制剂的2-甲基-4-苯基哌啶-4-醇衍生物和其使用方法
JP2025505645A (ja) 2022-02-08 2025-02-28 バーテックス ファーマシューティカルズ インコーポレイテッド Ａｐｏｌ１の阻害剤としてのスピロピペリジン誘導体およびその使用方法

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